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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands

Authors: María José Carlini, María Sol Recouvreux, Marina Simian, Maria Aparecida Nagai

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Progesterone receptor (PR) is expressed from a single gene as two isoforms, PRA and PRB. In normal breast human tissue, PRA and PRB are expressed in equimolar ratios, but isoform ratio is altered during malignant progression, usually leading to high PRA:PRB ratios. We took advantage of a transgenic mouse model where PRA isoform is predominant (PRA transgenics) and identified the key transcriptional events and associated pathways underlying the preneoplastic phenotype in mammary glands of PRA transgenics as compared with normal wild-type littermates.

Methods

The transcriptomic profiles of PRA transgenics and wild-type mammary glands were generated using microarray technology. We identified differentially expressed genes and analyzed clustering, gene ontology (GO), gene set enrichment analysis (GSEA), and pathway profiles. We also performed comparisons with publicly available gene expression data sets of human breast cancer.

Results

We identified a large number of differentially expressed genes which were mainly associated with metabolic pathways for the PRA transgenics phenotype while inflammation- related pathways were negatively correlated. Further, we determined a significant overlap of the pathways characterizing PRA transgenics and those in breast cancer subtypes Luminal A and Luminal B and identified novel putative biomarkers, such as PDHB and LAMB3.

Conclusion

The transcriptional targets identified in this study should facilitate the formulation or refinement of useful molecular descriptors for diagnosis, prognosis, and therapy of breast cancer.
Appendix
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Metadata
Title
Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands
Authors
María José Carlini
María Sol Recouvreux
Marina Simian
Maria Aparecida Nagai
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4550-z

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